Hydrochloric Acid → HCID 66930236, compound

HRID 2261238Notes

Reaction equation

HRID 2261238 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].C1C=NC2N(O)N=NC=2C=1.[ClH:28].Cl.[CH:30]([N:33]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)([CH3:32])[CH3:31].C(N(CC)C(C)C)(C)C.Cl>CN(C=O)C.C(Cl)Cl.C(Cl)CCl>[ClH:28].[CH:30]([N:33]1[CH2:39][CH2:38][CH2:37][N:36]([C:13]([C:12]2[CH:11]=[CH:10][C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[N:8][CH:7]=3)=[CH:17][CH:16]=2)=[O:15])[CH2:35][CH2:34]1)([CH3:32])[CH3:31]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 455958001-isopropyl-1,4-diazepane dihydrochlorideHCID 66930099HCID 66930099, compound

Product 1

HCID 66930236HCID 66930236, compoundYield 1.6%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(6-Cyano-3-pyridinyl)benzoic acid (D9) (0.35 g) was dissolved in dry DMF and treated with EDC (0.51 g) and a catalytic quantity of HOAT. The reaction mixture was stirred at rt for 5 min, followed by the addition of 1-(isopropyl)-hexahydro-1H-1,4-diazepine dihydrochloride (D2) (0.28 g) and N,N-diisopropylethylamine (1 ml), and allowed to stir at rt overnight. After evaporation of solvent the residue was partitioned between DCM (15 ml) and water (15 ml). The DCM layer was dried (magnesium sulfate) and concentrated to leave a crude residue which was purified by flash chromatography [silica gel, step gradient 0-15% MeOH (containing 10% 0.88 ammonia solution) in DCM]. Pure fractions were combined and concentrated to give the free base which was converted into the HCl salt in DCM (2 ml) with 1N ethereal HCl (1 ml). Evaporation of the solvents afforded the title compound (E15) (8 mg). 1H NMR δ (methanol-d4): 1.4 (6H, d, J=6.4 Hz), 2.16 (2H, bs), 3.47-4.2 (8H, m), 4.2-4.4 (1H, m), 7.68 (2H, d, J=8 Hz), 7.85 (2H, d, J=8 Hz), 7.98 (1H, d, J=8 Hz), 8.29 (1H, dd, J=8 Hz), 9.04 (1H, d, J=1.6 Hz). LCMS electrospray (+ve) 349 (MH+).

Workup

  1. stirringto stir at rt overnight
  2. customAfter evaporation of solvent the residue
  3. customwas partitioned between DCM (15 ml) and water (15 ml)
  4. dry with materialThe DCM layer was dried (magnesium sulfate)
  5. concentrationconcentrated
  6. customto leave a crude residue which
  7. customwas purified by flash chromatography [silica gel, step gradient 0-15% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  8. concentrationconcentrated
  9. customto give the free base which
  10. customEvaporation of the solvents

Sources & evidence

ORD record
ord-8be9618906164f9594dd128aca672e4b
Source dataset
uspto-grants-2010_12
Patent number
US07846922B2

Reaction notes

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